Abstract: The determination of the most stable conformers of a molecule can be regarded as a global optimization problem. The structure, characteristics, and behavior of a molecule are determined by molecular conformation. The most stable conformation is the global minimum of the molecular potential energy. However, in obtaining the global optimal value, the problem of finding the global minimum is highly complex and computationally difficult because of the number of local minima, which increases exponentially with the molecular size. A new variant of the cuckoo search algorithm with heterogeneous search strategies based on quantum mechanics, i.e., heterogeneous cuckoo search (HeCoS) algorithm is presented. The proposed HeCoS algorithm is applied to optimize a simplified molecular potential energy function. The results show that the HeCoS algorithm has powerful capability for searching the global minimum, fast convergence speed, good robustness, and better performance than other algorithms.